DILI DILI IDILI DILI DILI IDILI

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1 ACG * ACG DILI DILI IDILI HDS DILI DILI DILI IDILI DILI Understanding of ACG Clinical Guideline Diagnosis and Management of Idiosyncratic Drug-induced Liver Injury MAO Yimin. Shanghai Institute of Digestive Disease Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai Abstract DOI /j. issn The American College of Gastroenterology ACG released the first clinical guideline for drug-induced liver injury DILI in June 2014 the diagnosis and management of idiosyncratic drug-induced liver injury IDILI which includes all aspects of IDILI such as risk factors diagnosis differential diagnosis and treatment. The guideline discusses especially the issues on herbal and dietary supplements HDS induced liver injury and DILI in patients with chronic liver disease. The guideline is of great value for standardizing the clinical diagnosis and treatment providing the best recommendations for management of the patients with DILI. Since the evidence of research in the field of DILI is relatively weak at this moment the clinicians should consider the possible individual difference of the patients under the frame of guideline for making the best clinical decision. Key words Drug-Induced Liver Injury Idiosyncratic Drug-Induced Liver Injury Diagnosis Management Guideline LiverTox www. livertox. nih. gov HepaTox www. hepatox. org American College of Gastroenterology ACG DILI idio- HDS 1-2 syncratic DILI IDILI 4 drug-induced liver injury DILI DILI DILI DILI DILI 3 APAP * 2012ZX ZX

2 194 Chin J Gastroenterol 2015 Vol. 20 No. 4 DILI APAP DILI IDILI IDILI DILI APAP DILI DILI DILI HDS IDILI DILI 7 13 GRADE ALT ALT 13 DILI R R = ALT /ULN / ALP /ULN ALP IDILI ALT ALT 3 ULN IDILI R 5 ALP ALT ALP IDILI 2 ULNR 2 IDILI HLA 2 R 5 DILI HLA Roussel-Uclaf 5 Causality Assessment Method RUCAM HLA-B * 5701 DILI 80 6 structured expert opinion process SEOP DILI 8 SEOP DILI DILI DILI RUCAM

3 RUCAM DILI 3 DILI ALF DILI DILI DILI DILI DILI DILI DILI DILI 3 R DILI 1 HCV RNA 30 ~ 60 d ALT 2 50% IgM 3DILI d DILI Epstein-Barr 4 Wilson s Budd-Chiari DILI 50% DILI 180 d ALP DILI 2 DILI 1 CT DILI 2

4 196 Chin J Gastroenterol 2015 Vol. 20 No. 4 DILI DILI AASLD 2012 NAC DILI ALF 4 APAP ALF NAC 13 NAC DILI ALF > 5 ULN Hy s DILI ALF ALF NAC 7 DILI ALF FDA NAC DILI DILI DILI 1 ALT AST > CFDA 8 ULN 2 ALT AST > 5 ULN 2 3 ALT AST > 3 ULN > 2 INR > ALT AST > 3 ULN > 5% 5 DILI 20% DILI 14 DILI NAC FDA APAP 6 IDILI ALF DILI DILI HDS HDS DILIN HDS 2012 HDS HDS N- DILI FDA DILI NAC APAP ALF HDS DILI Ⅰ -Ⅱ HDS NAC 52% DILI 30% DILI n = 42 NAC 58% 27% 12 FDA NAC APAP HDS

5 HDS DILI 3 CLD DILI CLD 8 HDS DILI 9 HDS DILI 3 11 CLD DILI HDS HDS 10 HDS HDS 12 CLD HDS / 13 CLD DILI / / 4 ~ 6 DILI 6 DILI CLD DILI CLD DILI RUCAM CLD DILI CLD DILI CLD DILI DILI DILI DILI DILI CLD CLD DILI 1 Hoofnagle JH Serrano J Knoben JE et al. LiverTox a DILI CLD DILI ACG DILI IDILI website on drug-induced liver injury J. Hepatology CLD CLD 2. HepaTox

6 198 Chin J Gastroenterol 2015 Vol. 20 No. 4 J J. 10 Kleiner DE Chalasani NP Lee WM et al Drug-Induced Liver Injury Network DILIN. Hepatic histological 4 Chalasani NP Hayashi PH Bonkovsky HL et al Practice findings in suspected drug-induced liver injury systematic Parameters Committee of the American College of evaluation and clinical associations J. Hepatology 2014 Gastroenterology. ACG Clinical Guideline the diagnosis and management of idiosyncratic drug-induced liver injury Papay JI Clines D Rafi R et al. Drug-induced liver J. Am J Gastroenterol Daly AK Day CP. Genetic factors in the pathogenesis of drug-induced liver injury / /Kaplowitz N Deleve LD. Drug- Induced Liver Disease M. 3rd ed. San Diego Academic Press Daly AK Donaldson PT Bhatnagar P et al DILIGEN Study International SAE Consortium. HLA-B * 5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin J. Nat Genet J Lewis JH. Causality assessment Which is best -- expert opinion or RUCAM J. Clinical Liver Disease Rochon J Protiva P Seeff LB et al Drug-Induced Liver Injury Network DILIN. Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury J. Hepatology injury following positive drug rechallenge J. Regul Toxicol Pharmacol Lee WM Hynan LS Rossaro L et al Acute Liver Failure Study Group. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure J. Gastroenterology Squires RH Dhawan A Alonso E et al Pediatric Acute Liver Failure Study Group. Intravenous N-acetylcysteine in. pediatric patients with nonacetaminophen acute liver failure a placebo-controlled clinical trial J. Hepatology Navarro VJ Barnhart HX Bonkovsky HL et al. Herbal and dietary supplement induced hepatotoxicity in the US J. Gastroenterology Suppl 1 S http / /www. mmsp. cn